Prevention of Ototoxicity in NTM Patients Treated With IV Amikacin

Inclusion Criteria:

1. Providing informed consent, documented by signing and dating the currently validinformed consent form.

2. Considered by the Investigator to have unimpaired consent capacity, without relianceon a legally authorized representative.

3. Stated willingness and ability to comply with study procedures and availability forthe duration of the study.

4. Aged > 18 and < 80.

5. NTM infection meeting current Pulmonary NTM guidelines from the American ThoracicSociety and the Infectious Diseases Society of America (ATS/IDSA) for systemic (IV)aminoglycoside therapy.

6. Anticipated duration of IV amikacin treatment of at least 30 days at time of studyentry.

7. Statement of ability to take oral medication and adhere to the daily dosing regimen.

8. For females of reproductive potential: If they are of childbearing potential, theymust agree in writing to practice an effective double barrier method ofcontraception from the signing of the informed consent form until 1 month followingdiscontinuation of study drug treatment or agree to practice true abstinence, whenthis is consistent with the preferred and usual lifestyle of the subject.

9. For males of reproductive potential: Agree to practice effective barriercontraception from the signing of the informed consent form until 3 months (onespermatogenesis cycle) following the last dose of study drug or agree to practicetrue abstinence.

Exclusion Criteria:

1. Received a systemic aminoglycoside antibiotic within 6 months prior to planned firstdose of amikacin.

2. ECG at Screening or prior to randomization (mean of triplicate values) with QTinterval corrected using Fridericia's formula (QTcF interval) ≥ 450 msec.

3. ECG at Screening or prior to randomization with abnormalities that, in theInvestigator's judgment, might predispose patient to clinically significantarrhythmia.

4. Patients taking strong CYP3A4 inducers such as rifampin and rifabutin in the 7 daysprior to randomization or have the need for ongoing treatment with concomitant oralor intravenous therapy with strong CYP3A4 inducers during the study. If anadditional antibiotic is needed, then azithromycin will be used.

5. Patients taking strong CYP3A4 inhibitors such as clarithromycin in the 7 days priorto randomization or the need for ongoing treatment with concomitant oral orintravenous therapy with strong CYP3A4 inhibitors during the study. If an additionalantibiotic is needed, then azithromycin will be used.

6. Patients taking clofazimine or bedaquiline AND who also have congestive heartfailure, significant ventricular arrhythmia, uncorrected hypokalemia, or ECG (singleat Screening, mean of triplicate prior to randomization) showing QRS > 120 msec orheart rate < 50 bpm.

7. Patients with amikacin exposure within the 6 months prior to randomization.

8. Patients with known amikacin resistance (MIC >64)

9. Progressive liver disease (Child-Pugh B or C) which would affect or invalidateinterpretation of change from the baseline liver function tests over the course ofthe study.

10. Signs of disturbed integrity of the tympanic membrane, determined by otoscopy ortympanometry, including chronic perforation or middle ear or ear canal inflammationor effusion.

11. History of congenital hearing loss, otological surgery (excluding myringotomy tubesor simple tympanoplasty healed and currently intact), sudden hearing loss, orMeniere's disease.

12. Bilateral profound hearing loss (>90 Decibels [dB] HL) at all test frequencies.

13. Conductive hearing loss evidenced by average air-bone-gaps >15 dB HL for 0.25-4.0kilohertz (kHz)

14. History of active malignancy, either untreated or under active treatment.

15. History of risk factors for Torsades des Pointes (e.g., heart failure, hypokalemia,family history of Long QT Syndrome).

16. Venous access not adequate for performance of study procedures.

17. Presence of any circumstance, condition, ECG or laboratory finding that, based oninvestigator judgment, would interfere with study procedures or assessments orpresent to the patient an unreasonable risk from participation in this study.

18. Current or anticipated use of excluded concomitant medications as specified inSection 6.5.

19. Pregnant or lactating.

20. Female of childbearing potential who does not have a negative serum pregnancy testand does not agree in writing to using a double barrier method of contraception.

21. Female relying on menopausal status for contraception who does not haveFollicle-Stimulating Hormone (FSH) level consistent with that condition and who doesnot agree in writing to using a double barrier method of contraception.

22. Currently under correctional supervision (imprisoned, on probation or parole).